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Phase III Randomized Study of Letrozole in Women With Primary Breast Cancer Who Have Received 5 Years of Adjuvant Aromatase Inhibitor Therapy

Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Letrozole in Treating Women With Primary Breast Cancer Who Have Received 5 Years of Aromatase Inhibitor Therapy

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs
Phase III Treatment Active Not specified Other CAN-NCIC-MA17R
MA17R, NCT00754845

Objectives

Primary

To compare the disease-free survival of women with primary breast cancer treated with letrozole vs placebo after completing approximately 5 years (i.e., 4½ - 6 years) of aromatase inhibitor therapy (e.g., letrozole, anastrozole, or exemestane).

Secondary

To compare the effect of these drugs on overall (all cause specific) mortality of these patients.
To compare the incidence of contralateral breast cancer in patients treated with these drugs.
To evaluate the long-term clinical and laboratory safety of aromatase inhibitor therapy, particularly cardiovascular morbidity and mortality (e.g., significant coronary artery disease, including myocardial infarction and angina requiring percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal and nonfatal strokes, and all vascular deaths); incidence of all bone fractures (with particular emphasis on hip and wrist fractures as indicators of osteoporosis); changes in bone density; and common toxicities.
To compare overall quality of life (QOL) and menopausal-specific QOL of patients treated with these drugs.

Entry Criteria

Disease Characteristics:

Previously diagnosed with primary breast cancer

Must have received 4½ - 6 years of aromatase inhibitor therapy (e.g., letrozole, anastrozole, or exemestane), either as initial therapy or after prior tamoxifen citrate, including treatment received as part of clinical trial CAN-NCIC-MA17
- Completed aromatase inhibitor therapy ≤ 2 years ago

No metastatic or recurrent disease, contralateral breast cancer, or ductal carcinoma in situ in either breast, as determined by the following:
- Clinical examination of the breast area, axillae, and neck within the past 60 days
- Mammogram within the past 12 months*
- Chest x-ray within the past 60 days
- Bone scan, if alkaline phosphatase > 2 times normal and/or there are symptoms of metastatic disease AND confirmatory x-ray, if bone scan results are questionable, within the past 60 days
- Abdominal ultrasound, liver scan, or CT scan of the abdomen within the past 60 days, if ALT, AST, or alkaline phosphatase > 2 times normal
[Note: *A baseline mammogram is not required for patients who have undergone bilateral complete mastectomy]

Hormone-receptor status:
- Estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+) primary tumor at the time of diagnosis, defined as a tumor receptor content of > 10 fmol/mg protein or receptor positive by immunocytochemical assay (for patients not previously enrolled on clinical trial CAN-NCIC-MA17)
- ER+ and/or PR+ primary tumor OR hormone receptor status of primary tumor unknown (for patients previously enrolled on clinical trial CAN-NCIC-MA17)

Prior/Concurrent Therapy:

See Disease Characteristics
No concurrent selective estrogen receptor modulator (e.g., raloxifene, idoxifene)
No other concurrent anticancer therapy

Patient Characteristics:

Menopausal status not specified
ECOG performance status 0-2
Life expectancy ≥ 5 years
WBC > 3.0 x 10⁹/L OR granulocyte count (polymorphs + bands) ≥ 1.5 times 10⁹/L
Platelet count > 100 x 10⁹/L
AST and/or ALT < 2 times upper limit of normal (ULN)*
Alkaline phosphatase < 2 times ULN*
Able (i.e. sufficiently fluent) and willing to complete quality-of-life questionnaires in either English or French (NCIC CTG participating centers)
- Inability to complete questionnaires due to illiteracy in English or French, loss of sight, or other equivalent reason allowed
Accessible for treatment and follow-up
No other prior or concurrent malignancy except adequately treated, superficial squamous cell or basal cell skin cancer, carcinoma in situ of the cervix, or other cancer treated > 5 years ago that is presumed cured

[Note: *Elevated levels allowed provided imaging examinations have ruled out metastatic disease]

Expected Enrollment

1800

Outcomes

Primary Outcome(s)

Disease-free survival

Secondary Outcome(s)

Incidence of contralateral breast cancer
Overall survival
Long-term clinical and laboratory safety of aromatase inhibitor therapy, particularly cardiovascular morbidity and mortality, changes in bone mineral density, incidence of all bone fractures, and common toxicities
Quality of life (QOL) as assessed by SF-36 Health Survey and the Menopause-Specific QOL Questionnaire (NCIC CTG participating centers)

Outline

This is a multicenter study. Patients are stratified according to lymph node status at diagnosis (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), interval between last dose of aromatase inhibitor therapy and study randomization (< 6 months vs 6 months to 2 years), and duration of prior tamoxifen citrate use (0 vs < 2 years vs 2 - 4½ years vs > 4½ years). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy.

Arm II: Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy.

Patients undergo bone mineral density measurement by DEXA scan at baseline (if not done within 12 months of study entry), at 24 and 48 months during study therapy, and at the completion of study therapy. Some patients also complete quality-of-life questionnaires at baseline and at 12, 24, 36, 48, and 60 months.

After completion of study therapy, patients are followed annually.

Trial Contact Information

Trial Lead Organizations

NCIC-Clinical Trials Group

Paul Goss, MD, PhD, Protocol chair
Ph: 617-724-3118; 877-726-5130

Trial Sites

Canada

British Columbia

Kelowna

British Columbia Cancer Agency - Centre for the Southern Interior

Susan Ellard
Ph: 250-712-3922

Surrey

BCCA - Fraser Valley Cancer Centre

Gary K. Pansegrau
Ph: 604-930-4064

Vancouver

British Columbia Cancer Agency - Vancouver Cancer Centre

Stephen Chia
Ph: 604-877-6000

Victoria

British Columbia Cancer Agency - Vancouver Island Centre

Sharon Allan
Ph: 250-519-5570

Manitoba

Winnipeg

CancerCare Manitoba

Andrew L. Cooke
Ph: 204-787-1458

New Brunswick

Moncton

Doctor Leon Richard Oncology Centre

Pierre Whitlock
Ph: 506-862-4030

Moncton Hospital

Sheldon Rubin
Ph: 506-857-2881

Saint John

Saint John Regional Hospital

S. Eshwar Kumar
Ph: 506-648-6884

Newfoundland and Labrador

St. John's

Doctor H. Bliss Murphy Cancer Centre

Kara Laing
Ph: 709-777-8095

Nova Scotia

Halifax

Nova Scotia Cancer Centre

Daniel Rayson
Ph: 902-473-6106

Ontario

Hamilton

Margaret and Charles Juravinski Cancer Centre

Richard G. Tozer
Ph: 905-387-9495

Kingston

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Wendy Shelley
Ph: 613-544-2630

London

London Regional Cancer Program at London Health Sciences Centre

Francisco Perera
Ph: 519-685-8500

Mississauga

Carlo Fidani Peel Regional Cancer Centre at Credit Valley Hospital

Robert Myers
Ph: 905-813-1100

Newmarket

Southlake Regional Health Centre

Farrah Kassam
Ph: -

Oshawa

R. S. McLaughlin Durham Regional Cancer Centre at Lakeridge Health Oshawa

Jose Chang
Ph: 905-576-8711

Sault Ste. Marie

Algoma District Cancer Program at Sault Area Hospital

David Walde
Ph: 705-759-3815

St. Catharines

St. Catharines General Hospital at Niagara Health System

Brian Findlay
Ph: 905-684-7271

Sudbury

Northeastern Ontario Regional Cancer Centre

Pedro G. Lopez
Ph: 705-522-6237

Thunder Bay

Cancer Care Program at Thunder Bay Regional Health Sciences

Dimitrios Vergidis
Ph: 807-684-7204

Toronto

Edmond Odette Cancer Centre at Sunnybrook

Kathleen I. Pritchard
Ph: 416-480-4616

Humber River Regional Hospital - Weston

Jonathan J. Wilson
Ph: 416-249-4367

Mount Sinai Hospital - Toronto

Martin Blackstein
Ph: 416-586-5371

North York General Hospital - Ontario

Vivian Glenns
Ph: 416-498-4888

Princess Margaret Hospital

David Warr
Ph: 416-946-2260

St. Joseph's Health Centre - Toronto

Murray Davidson
Ph: 416-766-2365

St. Michael's Hospital - Toronto

Rashida Haq
Ph: 416-864-5912

Toronto East General Hospital

Yasmin H. Rahim
Ph: 416-469-3325

Trillium Health Centre - Mississauga Site

John A.P. Gapski
Ph: 416-521-4118

Windsor

Windsor Regional Cancer Centre at Windsor Regional Hospital

Caroline Hamm
Ph: 519-253-5253

Prince Edward Island

Charlottetown

Prince Edward Island Cancer Centre at Queen Elizabeth Hospital

Dagny Dryer
Ph: 902-894-2027

Quebec

Greenfield Park

Hopital Charles Lemoyne

Jean Latreille
Ph: 450-466-5009

Levis

Hotel-Dieu de Levis

Felix Couture
Ph: 418-691-5225

Montreal

CHUM - Hotel Dieu Hospital

Claude Potvin
Ph: 514-890-8000

Maisonneuve-Rosemont Hospital

Pierre Dube
Ph: 514-252-3822

McGill Cancer Centre at McGill University

Francois Patenaude
Ph: 514-934-1934

Quebec City

Hopital du Saint-Sacrement - Quebec

Jean Robert
Ph: 418-682-7511

Sherbrooke

CHUS-Hopital Fleurimont

Abdenour Nabid
Ph: 819-346-1110

Saskatchewan

Regina

Allan Blair Cancer Centre at Pasqua Hospital

Haji Ibrahim Chalchal
Ph: 306-766-2691

Saskatoon

Saskatoon Cancer Centre at the University of Saskatchewan

Ali El-Gayed
Ph: 306-655-2739

Related Information

PDQ® clinical trial CAN-NCIC-MA17

Registry Information

Official Title		A Double Blind Randomization to Letrozole or Placebo for Women Previously Diagnosed with Primary Breast Cancer Completing Five Years of Adjuvant Aromatase Inhibitor Either as Initial Therapy or After Tamoxifen (Including Those in The MA.17 Study)

Trial Start Date		2004-10-14

Trial Completion Date		2012-10-01 (estimated)

Registered in ClinicalTrials.gov		NCT00754845

Date Submitted to PDQ		2008-09-11

Information Last Verified		2009-05-20

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.